Background <p>Perinatal exposure to particulate matter 2.5 (PM_2.5) is linked to both neurotoxicity and childhood obesity. Given the role of inhibitory control in eating behavior, we propose that early-life PM_2.5 disrupts inhibitory control, contributing to obesity as part of a causal pathway.</p> Methods <p>In the PROGRESS cohort (<i>n</i> = 434) in Mexico City, we modeled ambient PM_2.5 exposure during pregnancy and the first year of life. Inhibitory control was assessed at age 4 using the Conners Kiddie Continuous Performance Test, and repeated adiposity measures were tracked from ages 4 to 8. We conducted latent profile analysis to identify profiles of inhibitory control and applied multinomial causal mediation analyses to estimate the natural total, direct, and indirect (i.e., mediated) effects of inhibitory control on the prenatal and first-year-of-life PM_2.5 exposure with childhood obesity-related outcomes, using separate models for each exposure window.</p> Results <p>Our analysis show a significant natural indirect effect between first-year postnatal PM_2.5 concentrations and greater body mass index (BMI) (<i>β</i> = 1.86 kg/m², 95%CI: 0.72, 3.19), BMI z-score (<i>β</i> = 0.11, 95%CI: 0.01, 0.25), and percent body fat (<i>β</i> = 3.04%, 95%CI: 1.26,5.04) at 8 years, and BMI change (<i>β</i> = 0.43 kg/m², 95%CI: 0.14, 0.80) from ages 4 to 8 years mediated through inhibitory control. No evidence of mediation by inhibitory control was found for prenatal PM_2.5 predicting obesity-related outcomes.</p> Conclusions <p>PM_2.5 exposure in the first year of life indirectly predicts childhood obesity through a pathway mediated by poorer inhibitory control. This new understanding of the underlying obesogenic mechanisms of air pollution can significantly inform policy and clinical interventions.</p>